1. Field of the Invention
The present invention relates generally to the field of medicine and pharmacology. More particularly, the present invention relates to compositions having therapeutic value comprising extracts of plant material from one or more of Glinus lotoides, Ruta chalepensis, Hagenia abyssinica and Millettia ferruginea. The compositions of the present invention are useful in the treatment and prevention of cancer and other diseases. The present invention further relates to methods of preparing such compositions, and methods for the treatment and prevention of disease by administration of the compositions to a patient in need thereof.
2. Description of Related Art
Herbal medicine involves the application of plants or plant parts, without chemical processing, as therapeutic agents for the treatment of human disease. The practice of herbal medicine can be traced back to the most ancient cultures, with some remedies known for thousands of years, and remains the primary form of medicine practiced by many groups today. Much of modem pharmacology is based on herbal medicine, with plant-derived compounds accounting for one quarter of pharmaceuticals (Foster, S, Duke, JA, Eastern/Central Medicinal Plants (Peterson Field Guides), Boston, Houghton Mifflin (1990), vii.). Common plant-derived pharmaceuticals include, for example, digoxin (Digitalis lanata), oral contraceptives (progestin derived from Diascorea villosa) and cephalosporins (Cephalosporium acermonium).
In the last twenty years, there has been a resurgence of interest in herbal medicine (Fugh-Berman, A., Clinical Trials of Herbs, in Primary Care 24: Complementary and Alternative Therapies in Primary Care, 889-903 (John L. Randall and Joel S. Lazar, eds.,1997)); (Lozoya, X., Ciba Found Symp (1994) 185: 130-40). Much of this interest is attributable to a growing awareness that the diversity of the plant kingdom represents a vast (and potentially endangered) resource for the discovery of novel pharmaceuticals (Akerele, O., World Health Forum (1993) 14: 390-5). One study, for example, notes that the 119 drugs of known structure that are produced commercially from plants account for only 90 species of higher plants (Farnsworth, N., Ciba Found Symp (1990) 154: 2-11). With estimates of the total number of species in the world""s flora ranging from 250,000 to 500,000 (and possibly greater), the possibilities are evident (Ayensu, E., Endangered Plants in the United States, Smithsonian Institution Press, 1978). The World Health Organization (WHO) has recognized this potential and made a significant policy commitment to encouraging the study of ethnobotany as a way to efficiently identify plants containing bioactive components.
Renewed interest in herbal medicine can also be attributed to another phenomenaxe2x80x94a growth of interest in complementary or alternative medicine (Eisenberg, D. et al., JAMA (1998) 280: 1569-75). Studies suggest that between 30 and 50 percent of the adult population in industrialized nations use some form of complementary and/or alternative medicine to prevent or treat a wide variety of health problems (Astin, J. et al., Arch Inter Med (1998) 158: 2303-10). Herbal medicine is among the most popular forms of complementary or alternative medicine, and its popularity has risen in parallel to that of complementary or alternative medicine. One study indicates that more than one third of Americans use herbs for health purposes (O""Hara et al., Arch Fam Med (1998) 7: 523-36). Medicinal plants and plant products may be used in lieu of mainstream therapies, but are often used in conjunction with traditional remedies. Herbal medicine is perhaps even more popular in Europe, where patients have been active in demanding natural alternatives to synthetic drugs (Harrison, P., CMAJ (1998) 158: 637-9).
The increased demand for herbal medicine reflects the public""s desire for more natural, effective or safer methods for treating disease. Widespread and increasing use of herbal remedies has been reported, for example, for inflammatory bowel disease (Rawsthorne, P. et al., Am J Gastroenterol (1999) 94: 1298-303); musculoskeletal disorders such as rheumatoid arthritis (Chandola, A. et al., J R Soc Med (1999) 92: 13-16; and HIV-related diseases (Ostrow, M. et al., J Acquire Immune Defic Syndr Human Retroviral (1997) 15: 115-20).
A variety of plants have been identified for their potential use as treatments for these diseases, among others. Plant extracts identified as potential HIV-inhibitors include, for example, Labiatae (Yamasaki, K. et al., Biol Pharm Bull (1998) 21: 29-33) Prunella vulgari (Yao, X. et al., Virology (1992) 187: 56-62); Coptis chineusis, Ligusticum wallichii, Illicium lanceolatum, Isatis tinctoria, Lonicera japonica, Salvia miltiorrhiza, Eyrcibe obstusifolia, Acanthopanax graciliatylus, Bostaurus domesticus, Scutellaria baicaleusis, and Inula helenium (U.S. Pat. No. 5,178,865). Chinese herbs, including Schizandrae, have proven beneficial in the treatment of chronic viral hepatitis (Sinclair, S., Altern Med Rev (1998) 3: 338-44).
Many herbal remedies are now being subject to clinical trials (Klepser, T. et al., Am J Health System Pharm (1999) 56: 125-38); (Fugh-Berman, A., Clinical Trials of Herbs, in Primary Care 24: Complementary and Alternative Therapies in Primary Care, 889-903 (John L. Randall and Joel S. Lazar, eds.,1997). Several medicinal plants have shown good results clinically, including Hypercium performatum (for depression); Allium sativum (hypercholesterolemia); Emblica officinalis (for hypercholesterolemia); Tanacetum parthenium (for migraines); Ginkgo bilboa (for dementia); Artemisia annua (for malaria and other parasites); Zingiber officinale (for nausea and emesis); and a variety of Chinese herbs (for HIV).
Perhaps nowhere is a greater desire for safer, more effective remedies seen than in the search for cancer treatments. An estimated 1.2 million new cases of invasive cancer will be diagnosed in the United States in 1999 (Landis, S. et al., CA Cancer J Clin (1999) 49: 8-31). Breast cancer alone will account for approximately 29% of these new cases. Plants and plant derived compounds have received attention as possible sources of novel therapeutics for cancer. Much of the work in this area is done under the auspices of the National Cancer Institute, which maintains an active screening program for medicinal plants (Cragg, G. et al., Ciba Found Symp (1994) 185: 178-90); (Cragg, G. et al., J Nat Prod (1993) 56: 1657-68). Plants and plant compositions identified as having potential for the treatment and/or prevention of cancer include extracts from the genus Geranium and Plantago and the species Calendula officinialis (PCT Application No. WO 98/24458); Peganum Harmala L. and Drakocephalum Kotshyi Boss. (PCT Application No. WO 99/24048); Echinops spinosus L. (PCT Application No. WO 99/24047); safflower extract (PCT Application No. WO 98/44005); Portulaca oleracea (PCT Application No. WO 98/24457); Agaricus blazei Murill (PCT Application WO 98/27992); Solanum muricatum (CSG) (Ren et al., Anticancer Res (1999) 19: 403-8); and Beta vulgaris (beet) (Kapadia et al., Cancer Lett (1996) 100: 211-4). Yet, the need for identification of suitable therapeutics remains high.
The present invention relates compositions and methods for the prevention and treatment of cancer and other diseases. The compositions of the present invention comprise extracts of plant material from Glinus lotoides, Ruta chalepensis, Hagenia abyssinica, and Millettia ferruginea, either alone or in combination. All four plants grow in the Waynadega region of Ethiopia where the rainfall is sufficient for vegetative growth. The use of at least several of these plants is known in indigenous cultures, though not in the form of the presently claimed composition nor for the claimed medicinal uses.
The plant Glinus lotoides, more commonly known as Mettre or, in Arabic, as Moghera, grows ubiquitously in the Allaqi area, south of Aswan, Egypt (Hamed et al., Phytochemistry (1996) 43: 183-188). Many species of the Glinus plant are eaten as green vegetables and possess a bitter flavor. Indigenously, Glinus lotoides serves a variety of medicinal purposes. It is used as an antiseptic, an anthelmintic, as a treatment for diarrhea and bilious attacks, and as a purgative for curing boils, wounds and pain in general. The juice of the plant is also sometimes given to weak children for strength (Hamed et al., Phytochemistry (1996) 43: 183-188). The use of Glinus lotoides to treat cancer has not yet been reported.
The plant Ruta chalepensis, also known as Tena Adam or rue, is a leafy, branched shrublet with an aromatic or pungent odor. The stems of the fully grown plants are two to three feet high. The leaves are compound (i.e., two or three times dissected) and are alternately arranged on the stems and branches. The yellowish-green flowers appear between February and May, followed by small, globular fruit. Ruta chalepensis is occasionally confused with Ruta graveolens (a distinct species) and vice versa. Key features known to distinguish Ruta chalepensis from Ruta graveolens include the shape of the leaves (elliptical vs. oblong), the margins of the petals (fringed vs. toothed), and the shape of the fruit lobes (pointed vs. rounded).
Medicinal uses of Ruta chalepensis are known, most often involving the aerial parts of the plant. In Saudi Arabia, for example, the aerial parts of the plant are used as a laxative, anti-inflammatory, antispasmodic, abortifacient, antiepileptic, emmenogogue, and to treat colic, headache, rheumatism, leucoderma and mental disorders (Shah et al., J Enthnopharmacol (1991) 34: 167-72); (Al-Said et al., J Ethnopharmacol (1990) 28: 305-312). In India, the plant is prescribed for dropsy, neuralgia, rheumatism, and menstrual and other bleeding disorders. The Chinese use a decoction of the roots as an antivenom and infuse the leaves with vinegar to treat children with convulsions and other nervous disorders. In Africa, an aqueous decoction of the leaves serves as a treatment for fevers. (Al-Said et al., J Ethnopharmacol (1990) 28: 305-312). Also of note, infusions of the leaves of the plant are know for use as stomach tonics, perspirants, and aborticides. Ruta chalepensis is also used, in combination with other herbs, in preparations for tooth and ear aches. The seeds of the plant, if taken with wine, have also been reported to provide an antidote for poisons. Ruta chalepensis is currently included on the FDA""s GRAS (Generally Recognized as Safe) list (www.ars-grin.gov/duke/syllabus/gras.htm).
Researchers have conducted scientific studies of Ruta chalepensis to investigate the various medicinal applications of the plant and to evaluate the potential toxicity and genotoxic effect of extended use of the plant product (Shah et al., J Enthnopharmacol (1991) 34: 167-72). However, no studies have yet reported the use of Ruta chalepensis as a cancer treatment.
Hagenia abyssinica, commonly known as Kosso, grows at high altitudes and is indigenous to East Africa, particularly Ethiopia. It is known to use a decoction of the female flower of Kosso as an anthelmenic (e.g., to expel intestinal worms, such as Tapeworms). The female flower is preferred over the male flower due to the more intense and unpleasant emetic effect of the male flower. ((Woldemariam et al., J Pharm Biomed Anal (1990) 8: 859-65). It can be prepared as an unstrained tea by steeping the powdered flowers in distilled water for 15 minutes (Starlight Herbal).
Various scientific studies have been performed with Hagenia abyssinica to evaluate its use an anthelminic, to determine the chemical components of the plant (Woldemariam et al., J Pharm Biomed Anal (1990) 8: 859-65), and to investigate potential toxicity resulting from prolonged use (Arragie, M., Ethiop Med J (1983) 21: 89-93); (Shah et al., J Ethnopharmacol (1991) 34: 167-72). The use of Hagenia abyssinica as an anti-cancer agent has not been reported. The antitumor potential of kossins, the phloroguinol components of the plant which constitute 3% of the weight of the female flower, has been reported (Woldemarian, T. et al., J Pharm Biomed Anal (1992) 10: 555-60).
The medicinal use of Millettia ferruginea, and more particularly its use as an anti-cancer agent, has not been previously reported.
It is an object of the present invention to provide a composition comprising an extract of plant material from one or more of Glinus lotoides, Hagenia abyssinica, Ruta chalepensis, or Millettia ferruginea for the treatment or prevention of cancer and other diseases.
It is a further object of the present invention to provide a pharmaceutical composition for the treatment or prevention of cancer and other diseases, which composition comprises an extract of plant material from one or more of Glinus lotoides, Hagenia abyssinica, Ruta chalepensis, and Millettia ferruginea and a pharmaceutically acceptable carrier or excipient.
Another object of the present invention is to provide a method for making a composition comprising an extract of plant material from one or more of Glinus lotoides, Hagenia abyssinica, Ruta chalepensis, and Millettia ferruginea suitable for use in the treatment or prevention of cancer and other diseases.
Another object of the present invention is to provide a method for making a pharmaceutical composition comprising an extract of plant material from one or more of Glinus lotoides, Hagenia abyssinica, Ruta chalepensis, and Millettia ferruginea and a pharmaceutically acceptable carrier, suitable for use in the treatment or prevention of cancer and other diseases.
It is a further object of the present invention to provide a method for the prevention and treatment of cancer and other diseases by administration of the compositions or pharmaceutical compositions of the present invention.
Additional objects and advantages of the present invention are set forth herein, or would be readily apparent to one skilled in the art.
The present invention relates to compositions comprising extracts of plant material from Hagenia abyssincia, Ruta chalepensis, Millettia ferruginea, or Glinus lotoides, either alone or in combination. The compositions of the present invention are useful in the treatment and prevention of cancer and other diseases. The compositions of the present invention include pharmaceutical compositions, comprising the extract or extracts in combination with a pharmaceutically acceptable carrier or excipient.
This invention also relates to a method for the preparation of the compositions of the present invention, including pharmaceutical compositions.
The present invention also relates to a method for preventing and or treating cancer or other diseases by the administration of the compositions of the present invention to a patient in need thereof. In particular, the present invention relates to a method of preventing or treating cancer, including breast cancer, prostate cancer, leukemia, melanoma and myeloma. The present invention further relates to a method of treating tuberculosis, diabetes, Parkinson""s disease, and various fungal and viral infections, including HIV.
The compositions and methods of the present invention advantageously provide beneficial preventative and/or therapeutic effects while providing a natural option to patients seeking an complementary and/or alternative therapies for disease.
The invention will be described in detail by reference to the attached drawings and to specific embodiments thereof, neither of which should be viewed as limiting the invention or the appended claims.